ALK-positive large B-cell lymphomas: A clinicopathologic study.

Background and Aim: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphomas (ALK+-LBCLs) are aggressive CD20-negative lymphomas, accounting for <1% of diffuse LBCLs. Being rare and with peculiar immunophenotypic characteristics, these can be easily misdiagnosed. We present 11 cases of ALK+-LBCLs diagnosed over a period of 11 years at a tertiary care hospital in South India to analyze the clinical, morphological, and immunophenotypic profile of these tumors. Subjects and Methods: ALK+-LBCL cases diagnosed from September 2009 to August 2020 were included. Clinical details were obtained from stored electronic records and summarized. Available hematoxylin and eosin (H and E) stained slides and immunohistochemistry slides were reviewed and observations tabulated. Results: Eleven patients (nine males and two females) were diagnosed with ALK+-LBCLs in the study period with seven presenting primarily with extranodal disease manifestations. Tumors in the lymph nodes showed diffuse architecture effacement and variable sinusoidal invasion. All tumors showed immunoblastic and plasmablastic-type large lymphoid cells with scattered anaplastic/multinucleate large cells, including rare Reed-Sternberg-like cells. Cytoplasmic granular ALK-1 staining, CD20 negativity, and immunohistochemical features of plasmablastic differentiation were noted in all. Of eight patients treated, only one achieved remission with multi-agent chemotherapy but relapsed after 6 months. Two patients died of disease and five others had progressive/persistent disease and were lost to follow-up. Conclusion: Although rare, these tumors should always be in the differential diagnoses of tumors with plasmablastic and immunoblastic morphology, especially in extranodal sites to avoid diagnostic delay/misdiagnosis.

Pathological prognostication of paediatric adrenocortical tumours: Is a gold standard emerging?

BACKGROUND: Criteria for the pathological classification of adult adrenocortical tumours (ACTs) have been found to overestimate the malignant potential of childhood ACTs. We sought to evaluate the accuracy and utility of criteria developed for paediatric ACT compared to current criteria for adults. METHODS: ACTs treated between January 2006 and December 2016 in two paediatric institutions were evaluated. Patients classified clinically as malignant (CM) had locally invasive disease at surgery requiring extensive en bloc resection to achieve clear margins, had local recurrence or distant metastasis. Slides were reviewed by pathologists blinded to the clinical outcome. A grade was assigned to each tumor according to the Weiss, Aubert, Wieneke and Dehner-Hill criteria. The pathological grade was compared to the clinical outcome. RESULTS: The median follow-up was 60 months (interquartile range 25-80 months). Based on clinical criteria, of 22 patients 14 (64%) had a benign course and eight (34%) behaved malignant. The malignant potential was overestimated by Weiss criteria in 23% and Aubert criteria in 27%. Wieneke and Dehner-Hill criteria showed good clinicopathological correlation; no child who had a benign course was classified as malignant. The Dehner-Hill criteria, however, classified five (23%) children as intermediate risk of which three had a clinically benign and two a CM course. CONCLUSION: The Wieneke criteria accurately predicts the clinical course in childhood ACTs and could be considered the gold standard in their pathological characterization.

Presurgical Screening of Fine Needle Aspirates from Thyroid Nodules for BRAF Mutations: A Prospective Single Center Experience.

OBJECTIVE: Analysis of BRAF V600E mutation in thyroid fine needle aspirates (FNA) is an important adjunct to cytology, particularly among FNA placed in the "indeterminate category." However, such a prospective evaluation of FNA obtained from patients with thyroid nodules has been lacking from India. MATERIAL AND METHODS: FNA from 277 patients were prospectively evaluated for BRAF mutations by Sanger's sequencing. A subset of 30 samples was also analyzed by pyrosequencing using the PyroMark BRAF mutation kit. RESULTS: Overall, 27.2% of FNA samples were positive for mutations including 19 (35.8%) of the 53 histologically confirmed papillary thyroid carcinoma (PTC), 2 of the 25 follicular variants of PTC, and 1 anaplastic thyroid carcinoma. Only 1 (2.7%) of the 37 samples in the atypia of undetermined significance/follicular lesion of unknown significance category was BRAF positive. The sensitivity of cytology improved marginally from 67.1% to 68.3% when evaluated with BRAF. Further, a comparison of the clinicopathological characteristics of BRAF positive and negative PTCs showed a significant association (P = 0.05) between lymph node metastasis and BRAF positivity. CONCLUSION: BRAF positivity was lower than that reported from East Asia with the test being useful in confirming malignancies among the suspicious of malignancy and malignant categories.

Extramedullary plasmacytoma: an unusual neoplasm in a HIV-positive patient.

There is a wide range of plasma cell abnormalities in people living with HIV (PLHIV). Extramedullary plasmacytomas are not common in HIV infection, unlike plasmablastic lymphomas. An HIV-positive 44-year-old man on antiretroviral therapy presented with a rapidly progressing swelling on the face. Imaging revealed underlying bone destruction. Histologically, there was a tumour composed of small to medium-sized plasmacytoid cells admixed with many mature plasma cells and plasmablasts. These were positive for CD138 and MUM 1. Extramedullary multiple myeloma was ruled out as CD56 and cyclin D-1 were negative. EBV was negative. As the tumour cells were mostly mature, plasmablastic lymphoma was also excluded. The presence of a monoclonal protein (1 g%), IgG kappa type, was detected. Neoplasia of plasma cells acquires special clinical characteristics in PLHIV. These patients are younger, with a greater tendency to develop solitary extramedullary plasmacytomas with atypical clinical evolution and greater aggressiveness of the neoplastic process. All of these features, along with a high proliferation index (MIB1 60%) was found in our patient. We report this case for its rarity, histopathological dilemma and its atypical features in HIV infection.

Primary pigmented nodular adrenocortical disease.

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent Cushing's syndrome and has characteristic gross and microscopic pathologic findings. We report a case of PPNAD in a 15-year-old boy, which was not associated with Carney's complex. Bilateral adrenalectomy is the treatment of choice.

Renal cell carcinoma associated with granulomatous reaction.

Granulomatous inflammation is a distinctive pattern of chronic inflammatory reaction characterized by accumulation of epithelioid histiocytes and multinucleate giant cells. The cause of granulomas can be infectious or non-infectious. Granulomas have been described within the stroma of malignancies like carcinomas of the breast and colon, seminoma and Hodgkin's lymphoma, where they represent T-cell-mediated reaction of the tumor stroma to antigens expressed by the tumor. Granulomatous reaction in association with renal cell carcinoma (RCC) is uncommon, with only few published reports in the literature. We describe three cases of conventional (clear cell) RCC associated with epithelioid granulomas within the tumor parenchyma.

Large clear cell tumor of the lung mimicking malignant behavior.

An 18-year-old man presented with a large (12 x 10 cm) cystic mass involving the lower lobe and lingula of the left lung on computed tomography. Intraoperatively a large cystic mass was seen densely adherent to the left lung and the chest wall. A left pneumonectomy was performed because of the dense adhesions and extreme vascularity. Pathologic examination revealed a benign sugar cell tumor of the lung. We believe this is the first case report of such a large, clear cell tumor of the lung, mimicking malignant behavior in terms of vascularity and local invasion and requiring pneumonectomy.